Psychomotor stimulant drugs of abuse cause brain damage that is dependent on elevated body temperature. This year, we continued to examine brain and body temperature changes in relation to the permeability of brain-blood barrier during exposure to meth-amphetamine. We found that meth-amphetamine induces the leakage of brain-blood barrier and the degree of this leakage depends on drug-induced increase of brain temperature. This year, in collaboration with Dr. Sharma (Uppsala University, Sweden), we examined the passage of different molecules from the periphery to the brain during methamphetamine intoxication. The substance of special interest was gp120, a neurotoxic protein that appears in circulation during AIDS. Although this protein fails to enter the brain in normal conditions, it can cross the blood-brain barrier during methamphetamine intoxication. If this mechanism will be confirmed (data is analysis), it will explain high probability of neuroAIDS and progressive neurodegeneration often developed in methamphetamine users. We also continue our studies of the central mechanisms underlying addictive properties of cocaine and its physiological effects. Particularly, we examined neuronal effects of iv cocaine with those induced by cocaine methiodide, a cocaine s derivative that fails to cross blood-brain barrier. We found that both drugs have similar excitatory effects of central neurons, implicating peripheral K+ and Na+ channels as an important substrate involved in mediating the acute stimulatory effects of iv cocaine. Our thermorecording work was supplemented by parallel electrophysiological studies, using single-unit recording with iontophoresis in awake rats. This approach appears to be an important tool for the study of central mechanisms of action of various drugs of abuse and drug-taking behavior. It provides novel information to examine the role of environmental factors in adverse health effects of addictive drug use.